The problem of heterogeneity in both the dynamics of the proliferation and in the chemical constitution of human diploid fibroblasts is central to the resolution of the phase III phenomenon. The presence of nondividing cells in low PDL cultures and rapidly dividing cells in high PDL cultures confounds the understanding of the in vitro aging process in mass culture. The existence of techniques to separate cells based on a variety of chemical, physical or behavioral characteristics and the considerable array of distinguishing differences between young and old cells and cultures make it appropriate to begin such work. We propose to exploit advances in flow sorting, and selective synchrony methodologies such as mitotic selection and centrifugal elutriation to prepare populations of human diploid fibroblasts with reduced temporal and constitutional heterogeneity. Using populations with better defined origins we hope to determine the pathway or pathways leading to senescence and will make attempts to reduce or enhance phase III onset.